Salivary agglutinin (SAG) is a mucin-like glycoprotein which plays an important role in modulating streptococcal colonization of oral tissues. SAG immobilized on tissue surfaces may promote streptococcal adherence while soluble SAG aggregates streptococci and may function in clearance of these organisms from the mouth. The S. sanguis and S. mutans receptors for SAG are calcium dependent lectins which exhibit considerable sequence and structural similarity. However, carbohydrate binding specificity of these proteins is species specific. We are interested in defining the molecular basis of carbohydrate binding specificity and the role of calcium in the interaction of these lectins with SAG. In the present application, we propose to identify the specific lectin domains involved in sugar recognition and calcium binding. the dependency of lectin activity of calcium will be investigated by monitoring the carbohydrate binding capacity of lectins in which calcium binding sites have been inactivated by site specific mutagenesis. We will also evaluate the structural and functional similarities of SAG receptors from other oral streptococci. Finally, the cloned lectins will be utilized as affinity resins to identify and characterize the specific carbohydrate structures of SAG which are recognized by the S. sanguis and S. mutans lectins. An understanding of how structural variation influences function within a group of related proteins is clearly important for the rational design of therapeutics and potential vaccine candidates. This appears especially pertinent for oral streptococci, where bacterial/host interactions of both pathogenic and non-pathogenic organisms are mediated by highly similar proteins.